1. Field of the Invention
The present invention relates to a precursor of a tissue regenerating instrument and to a method of producing a tissue regenerating instrument.
2. Description of the Related Art
When a tissue such as a nerve or tendon of a human is damaged due to an accident, a disaster or a disease and can not be healed by self resilience, disorders in perception, sensation, and exercise capacity of a patient is occurred. To such a patient, a medical care may be performed in which after the damaged portion is excised, a tissue is collected from another site of the body of the patient and transplanted to the excised portion. Such an operation is called autotransplantation. Since in autotransplantation a healthy tissue which is not damaged is collected, the extracted portion may cause disorders in perception, sensation and mobility in the site.
Accordingly, various studies have been developed with medical cures in which an instrument provided with a foothold for cell growth is implanted in the excised site to allow cells to grow from an end of the tissue along the foothold, thereby regenerating the tissue and recovering the function of the tissue. These are studies as part of so-called regenerative medicine and such an instrument is called scaffold. The instrument includes, as a major construction, a tube that prevents other cells from invading from outside and a guiding member that is inserted in the lumen of the tube and guides nerve cells to grow in a longitudinal direction.
In studies of regenerative medicine using a scaffold, one skilled in the art would consider incorporating a drug or cell in the instrument, who relies on a special function of cells without thorough consideration. However, such an instrument having incorporated therein a drug or cells not only increases cost prices of the instrument but also requires physicians with extra efforts from the viewpoint of storage and safety management. Further, physicians must have knowledge and technique to handle the drug or cell. Therefore, those physicians who have no such knowledge and technique can not handle the instruments.
For example, the nerve regenerating tube described in WO 1998/022155 is very difficult to handle since the tube uses a gel containing collagen, laminin or the like. This is because gel is fluid and has an unstable shape. Further, since the moisture in the gel penetrates into collagen, the collagen is decomposed even if the collagen is crosslinked. In such cases, the instrument can not be stored for a long period of time.
Further, the nerve regeneration tube described in JP 2005-143979 A is seeded with Schwann cell. This can be handled only by physicians who have knowledge and technique for handling cells.
In view of the present state of the above-mentioned regenerative medicine, the inventors of the present invention have made extensive studies on development of regeneration instruments that do not handle cells. As a result, they have invented a collagen-made tissue regenerating instrument (JP 2002-320630 A). Such an instrument is wholly constituted by collagen, a material which is decomposed and absorbed in a living organism and in addition uses no compound such as a crosslinking agent, so that the instrument is safely decomposed and absorbed in a living organism. Further, surprisingly, the instrument allows a tissue to be regenerated without incorporating a special cell. That is, there is no need to handle a drug or cell, so that manufacturers can produce this instrument at low cost. Further, the produced instrument will not be decomposed or deteriorated for a long period of time. Any physician who has a general surgery technique can easily perform treatment with this instrument.
Next problem in development of this instrument is to improve added value by improving handleability. Thus, the improvement of additional value does not mean incorporation of a drug or cell in the instrument as described above, but improvement in the handleability of the instrument. Here, an instrument having a shape which is the easiest for physicians to handle may be an instrument having a collagen tube provided with a lumen therein, with a space being provided in both ends of the lumen.
For example, if the instrument is flat on both ends of the instrument as described in WO 1998/022155 and JP 2005-143979 A, physicians must use end-to-end suture, which is an extremely high level technique of suture, to suture the instrument and the tissue. In addition, when the instrument and the tissue are sutured, an end of the instrument and an end of the tissue are just in abutment, so that there is the possibility that the cells of the tissue may grow on outer wall of the instrument.
On the other hand, if an instrument provided with a space for inserting a tissue end in each lumen in advance is produced, the length of the tissue to be regenerated is not constant, so that the instrument can be used only for regeneration of a limited tissue. For this reason, the instrument must be cut so as to match the length of the tissue to be regenerated. However, of course, the cut surface is flat.
The inventors of the present invention have disclosed a nerve regeneration inducing tube having a space in which a tissue end is inserted on at least one end of the tube (JP 2004-208808 A). Such an instrument is cut so as to match the length of a nerve to be regenerated. The instrument can be implanted after an end of a nerve on the side of the central nerve is inserted in the space. However, the end of the nerve on the peripheral nerve end will be for a flat end. Since no cell grows from the peripheral nerve, the bad effect that cells grow on the outer surface of the instrument can be prevented but still end-to-end suture must be performed for suturing a nerve and an instrument.
Generally, such an instrument may be improved in handleability of the instrument by swelling with a softening solution such as physiological saline before implantation. However, in the instruments disclosed in above-mentioned Patent Documents, the inducing member is fully packed in the lumen of the tube, the penetration rate of the softening solution such as physiological saline is insufficient, so that it takes a long time until saturated swelling state is reached. Further, the inducing member has an outer diameter larger than an inner diameter of the tube by swelling, so that the tube may be deformed or broken. Even when the tube is not deformed or broken, high friction occurs between the inner wall of the tube and the inducing member, which makes difficult production of an instrument provided with a space for inserting a tissue end in the lumen on both ends.
In addition, there arises also the problem that when the inducing member is packed in the lumen of the tube, operation of inserting the inducing member in the lumen of the tube is cumbersome in the production step of the instrument. In particular, the inducing member in the instrument disclosed in Patent Document 2 is a bundle of a plurality of filaments, so that the ends of the inducing members is not aligned. Therefore, during the operation of inserting the inducing member in the lumen of the tube, a portion of the filament bundle could get hung on an end of the tube, which makes the operation cumbersome.